川陈皮素对糖尿病肾病大鼠AMPK和eNOS表达的影响研究

【摘要】目的 观察川陈皮素对糖尿病肾病大鼠的治疗作用，并从腺苷酸蛋白活化激酶（AMPK）和内皮型一氧化氮酶（eNOS）途径探讨其作用机理。方法 采用高脂高糖饲料喂养+链脲佐菌素（STZ）腹腔注射复制2型糖尿病肾脏损害大鼠模型，模型构建成功后，将其随机分为正常组、模型组、贝那普利干预组以及川陈皮素低、中和高剂量治疗组（n=20）。实验中密切监测大鼠一般情况，治疗期结束后收集尿液检测24h蛋白尿，收集血液检测肾功能指标、抗氧化指标，收集肾脏观察肾脏病理学，同时检测肾脏组织中AMPK及eNOS蛋白和mRNA的表达结果。结果 正常组肾小球正常，无明显病理特征；模型组出现肾小球增大，系膜和肾间质纤维组织增生；贝那普利组和川陈皮素三个剂量组相较于模型组明显减轻。与正常组相比，模型组24h尿蛋白定量、UREA、CREA和MDA明显升高(P＜005)；SOD和GSH明显降低(P＜005)，与模型组相比，贝那普利和川陈皮素三个剂量组24h尿蛋白定量、UREA、CREA和MDA明显降低(P＜005)，SOD和GSH明显升高(P＜005)。与正常组相比，模型组p AMPK、AMPK和eNOS蛋白和mRNA表达均明显降低(P＜005)；与模型组相比，贝那普利组和川陈皮素低、中和高剂量组AMPK和eNOS蛋白和mRNA表达明显升高(P＜005)。结论 川陈皮素可保护肾功能，提高血清和肾脏抗氧化指标，同时增加AMPK和eNOS蛋白和mRNA表达，最终保护糖尿病肾脏损害。     

梗阻性黄疸高危因素分析

目的 :通过探讨梗阻性黄疸临床指征 ,了解其病程中的高危因素。并及时降低并发症及死亡率 ,提高临床疗效。方法 :对我科 1993年— 2 0 0 0年收治的 2 92例梗阻性黄疸病人进行性分析 ,统计年龄、梗阻时间、性质、手术时间 ,入院 2 4小时内测尿素氮 (BUN)、白蛋白 (A)、总胆红素(TBIL)、白细胞 (WBC)、血红素 (HB)、腹水 ,分析其高危因素。结果 :年龄 >6 5岁并发症发生率为2 5 .2 0 % ,病死率 3.2 5 % ;梗阻时间超过 2 0天以上者 ,并发症 2 8.87% ,病死率 5 .15 % ;肝功能Child氏B级、C级者 ,并发症发生率为 2 9.2 0 % ,病死率为 5 .31% ,延期手术并发症发生率为 2 9.4 1% ,病死率为 4 .90 %。结论 :梗阻性黄疸病人年龄越大 ,梗阻时间越长 ,肝功能越差 ,不及时手术是各种并发症发生及病死率增高的高危因素     

Scofix系统治疗特发性脊柱侧弯18例

青少年特发性脊柱侧弯是临床上比较常见的一种脊柱畸形 ,自 1998年 4月 - 2 0 0 2年 4月 ,我们采用Scofix内固定加植骨融合术治疗 18例 ,经随访 1～3年 ,疗效满意 ,现报告如下。1　临床资料　　本组 18例 ,男 8例 ,女 10例 ;年龄 11～ 16岁 ,病程 4个月～ 12年。按照国际脊柱侧弯研究会推荐的King方法分型[1] :Ⅰ型 2例 ;Ⅱ型 4例 ;Ⅲ型 7例 ;Ⅳ型 5例。脊柱侧弯及旋转按Cobb角及More法定量评估并计算弹性指数 :Cobb角为 4 0°～ 70° ,平均 5 2° ;旋转 0°～ 3° ,平均 2° ;弹性指数 10 %～ 38% ,平均2 9 %。所有病例手术均一次完成。2…     

大鼠脊髓缺血再灌流时脊髓神经元对躯体和内脏传入刺激的反应

５０只大鼠用乌拉坦麻醉，箭毒制动。通过阻断腹主动脉血流以模拟腰段脊髓的局部缺血和再灌流损伤，玻璃微电极记录Ｌ２节段脊髓单位放电（ＳＣＵＤｓ），观察缺血再灌流时脊髓神经元对腓神经刺激（ＰＮＶ），内脏大神经刺激（ＶＬＮＶ）及两者同时刺激（ＳＶ）的反应。结果在缺血前所记录的１３３个自发放电单位中，对３种刺激均产生兴奋（Ｅ）、抑制（Ｉ）及无反应（ＮＲ）３种形式的反应，表明大鼠Ｌ２节段脊髓存在躯体、内脏和躯体内脏反应性神经元，并有会聚和阻塞现象。在脊髓缺血再灌流时，神经元对ＰＮＶ、ＶＬＮＶ、ＳＶ也产生Ｅ、Ｉ、ＮＲ３种形式的反应，提示脊髓缺血再灌流时神经元对躯体和内脏传入刺激的反应形式不受影响；但缺血时ＳＣＵＤｓ对ＰＮＶ、ＶＬＮＶ产生反应的单位数减少，这表明脊髓缺血损伤时神经元对躯体和内脏传入刺激的反应性减弱，随着缺血损伤加重，脊髓神经元对躯体内脏信号的整合功能下降     

Prophylactic use of chlorpromazine to improve survival of random skin flaps in pigs

On the basis of earlier success in rat studies, chlorpromazine was evaluated as a probable agent for improving survival of random skin flaps in pigs. The aim was to exclude the possibility that the effect of the chlorpromazine is species specific and to find out if it is dose dependent. One hundred and five dorsally-based 12×4 cm flaps were raised unilaterally on the backs of 15 pigs. The animals were divided into three groups using 15 mg/kg chlorpromazine, 7.5 mg/kg chlorpromazine, and a saline-treated control group. Flaps in the control group averaged 40.57±3.17% necrosis, while flaps in the 15 mg/kg and 7.5 mg/kg chlorpromazine-treated groups averaged 31.53±4.77% and 11.47±2.22% necrosis respectively. These results demonstrate dose dependent beneficial affects of chlorpromazine and the survival of random skin flaps in the pig. Although ideal dose levels are still to be determined, flap survival improved with the prophylactic use of chlorpromazine at the lower 7.5 mg/kg dosage.     

Comparison of positive allergy skin tests among asthmatic children from rural and urban areas living within small geographic area.

BACKGROUND: Evidence of increased asthma and allergic response among urban versus rural residents has been reported. OBJECTIVE: To evaluate the prevalence of allergic response among asthmatic children from urban and rural areas living within close proximity. METHODS: In all, 448 asthmatic children from urban (363) and rural (85) areas were studied. The study group consisted of 234 9-year-olds and 214 12-year-olds. A health questionnaire was completed on each child who subsequently underwent allergic skin prick tests (SPTs). RESULTS: There was significantly more positive SPT response to house-dust mite, mold, cat, and cypress among asthmatic children from urban areas compared with children living in rural areas: 58.3% versus 37.6%, 46.1% versus 31.8%, 17.45 versus 5.9%, and 26.2% versus 15.3%, respectively. Positive SPT for indoor allergens were significantly greater among asthmatic urban residents than asthmatic rural residents: 63.3% versus 45.5%, respectively (P < 0.02). Positive SPT response to all the allergens checked was higher among the 12-year-old age group when compared with the 9-year-olds, 34.6% versus 22.7%, respectively (P = 0.05). CONCLUSIONS: Allergic response measured by SPT is significantly more common among asthmatic children from urban areas as opposed to rural, even though both areas are within small distance of one another. Further, asthmatic children living in urban areas demonstrated more allergic response to both indoor and outdoor allergens. The allergic response tends to increase with increased age in both urban and rural asthmatic children.     

Skin injury following contact with a complex amine

Eight patients with skin damage due to contact with an amine are described. The material is used in the potash industry under the commercial name of Armine to prevent bosselation. Although it is considered to be a strong base, no deep burns were encountered. The reaction to this material initially resembled a dermatitis; later the wound developed the typical appearance of a burn. In addition to the common conservative treatment, antihistamine drugs were used. When a true allergic reaction was suspected steroids were added to the regimen.     

Anti-RMA: a murine monoclonal antibody that activates rat macrophages. I. Distribution and characterization of the RMA antigen.

Activated macrophages participate in inflammation by eliminating foreign cells, promoting wound healing, and modulating the immune response. A murine monoclonal antibody, designated anti-rat macrophage activator (RMA), was raised against alveolar macrophages (AM) activated with interferon-gamma (IFN-gamma) and phorbol myristate acetate (PMA). The RMA antigen is expressed by resident macrophages but not by other cells. Binding to AM by anti-RMA is not competitively inhibited by the murine monoclonal antibodies MRC OX-41, OX-42, and OX-43. Surface membrane expression of RMA antigens is upregulated by lipopolysaccharide, PMA, and tumor necrosis factor-alpha but not by IFN-gamma. Stimulation of AM with anti-RMA yields distinct ultrastructural alterations, as well as de novo protein and DNA synthesis. Immunoprecipitation of [35S]methionine metabolically labeled AM yields a 120 kD protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that is not altered by chemical reduction. We conclude that the RMA antigen is macrophage specific and that binding of anti-RMA to AM promotes functional activities in a subset of these cells.     

Anti-RMA, a murine monoclonal antibody, activates rat macrophages: II. Induction of DNA synthesis and formation of multinucleated giant cells

Anti-RMA is a murine anti-rat monoclonal antibody that binds to a 120-kD surface membrane antigen expressed primarily by alveolar macrophages. Saline-lavaged alveolar macrophages (AM) formed clusters after incubation with anti-RMA. Anti-RMA produced multinucleated giant cells (MGC) in approximately 15% of adherent AM, and the F (ab')2 fragment of anti-RMA yielded MGC in approximately 9% of AM. The Fab fragment of anti-RMA did not promote MGC formation, nor did the murine anti-rat monoclonal antibodies OX41 and W3/25 (anti-CD4). Although anti-RMA produced a tenfold increase in [3H]thymidine incorporation by AM, it yielded a minimal increase in the number of AM. Autoradiography of AM stimulated with anti-RMA showed heterogeneous labeling of nuclei in MGC, suggesting that 3H-labeled AM may fuse with AM that are not actively synthesizing DNA. These findings suggest that binding of anti-RMA to AM may activate DNA synthesis, and promote clustering and fusion of AM, leading to MGC formation.     

胰腺癌细胞通过高表达核因子E2相关因子2促进巨噬细胞血管内皮生长因子表达的实验研究

目的探讨胰腺癌细胞对巨噬细胞血管内皮生长因子(VEGF)表达的影响及核因子E2相关因子2(Nrf2)在其中的作用。方法检测单一人胰腺癌细胞(PANC-1)培养组、单一巨噬细胞培养组、肿瘤细胞和巨噬细胞共培养组中各细胞VEGF表达。利用野生组、Nrf2过表达组、Nrf2敲减组中PANC-1的条件培养基刺激巨噬细胞,检测巨噬细胞VEGF的表达。将Nrf2过表达PANC-1条件培养基分为乳酸正常组,乳酸减低组和乳酸减低恢复组利用各组条件培养基刺激巨噬细胞,探究乳酸在抑制巨噬细胞VEGF表达中的作用,并且检测乳酸可能激活的巨噬细胞内的信号通路。两组间相关性采用费舍尔检验,两组间比较采用独立样本t检验,多组间比较采用单因素方差分析。结果肿瘤细胞与巨噬细胞共培养组中巨噬细胞VEGF表达高于其他各组中各细胞,差异有统计学意义(F=99.836,P<0.05)。Nrf2过表达的PANC-1条件培养基刺激组中巨噬细胞VEGF相对表达量为2.875±0.446,分泌水平为(326.744±27.507)ng/L,显著高于其他组,差异有统计学意义(F=26.952、48.996,P<0.05)。Nrf2过表达组中PANC-1乳酸分泌高于对照组,差异有统计学意义(t=5.974,P<0.05)。调节Nrf2过表达PANC-1条件培养基中乳酸浓度,利用条件培养基刺激巨噬细胞,乳酸减少组中巨噬细胞内活性氧物质(ROS)生成显著低于其他组,差异有统计学意义(F=26.952,P<0.05)。抑制巨噬细胞内ROS,抑制组VEGF表达(0.582±0.063)和分泌量[(156.560±23.200)ng/L]显著减少,差异有统计学意义(t=4.791、7.333,P<0.05)。结论Nrf2通过增加胰腺癌细胞乳酸分泌诱导巨噬细胞内ROS生成,从而促进巨噬细胞VEGF表达。